三阴性乳腺癌（TNBC）是一种具有高度异质性、侵袭性且预后较差的恶性肿瘤，这与其代谢可塑性及有限的治疗靶点有关。我们前期研究发现LASS2过表达增加MDA-MB-231细胞mtROS，抑制其侵袭能力，但分子机制不明。进一步研究率先发现LASS2可能通过线粒体复合物/OXPHOS激活AMPK信号调控脂肪酸合成和氧化，提示LASS2可能与线粒体能量代谢有关。基于此，我们假设LASS2通过线粒体复合物/OXPHOS介导AMPK/HIF-1信号抑制TNBC的侵袭转移。本研究拟以TNBC临床肿瘤组织样本、不同TNBC细胞、荷瘤小鼠模型进一步探讨LASS2抑制TNBC侵袭转移的分子机制，研究内容主要涉及：①明确LASS2对TNBC侵袭转移、线粒体代谢的作用；②运用荷瘤小鼠模型评价LASS2抗肿瘤效力；③阐明LASS2通过线粒体复合物/OXPHOS抑制TNBC分子机制。这将为TNBC靶向治疗提供新思路。

Triple negative breast cancer (TNBC) is a malignant tumor with high heterogeneity, invasiveness and poor prognosis, which is related to its metabolic plasticity and limited therapeutic targets. In our previous studies, we found that overexpression of LASS2 increased the production of mtROS and inhibited the invasive ability of MDA-MB-231 cells, but the molecular mechanisms remain unclear. Further studies first found that LASS2 might inhibit fatty acid synthesis and oxidation through AMPK signaling pathway mediated by interacting with mitochondrial complexes/OXPHOS, suggesting that LASS2 may be related to mitochondrial energy metabolism. Based on this, we hypothesized that LASS2 suppresses the invasion and metastasis ability of TNBC through AMPK/HIF-1 signaling pathway mediated by interacting with mitochondrial complexes/OXPHOS. In this study, TNBC clinical tumor tissue samples, different TNBC cells and nude mice tumor-bearing models were used to further explore the molecular mechanisms of LASS2 inhibiting the invasion and metastasis ability of TNBC. The main contents of the study are as follows: ①To clarify the effect of LASS2 on the invasion and metastasis ability and mitochondrial metabolism in TNBC cells or tumor tissue; ②To evaluate the anti-tumor effect of LASS2 by using nude mice tumor-bearing models; ③To elucidate the molecular mechanisms that LASS2 inhibits TNBC through mitochondrial complexes/OXPHOS. This will provide new ideas for molecular targeted therapy for TNBC.